Keehn Connie A, Smoller Bruce R, Morgan Michael B
Department of Pathology, University of South Florida College of Medicine, USA.
Mod Pathol. 2003 Aug;16(8):772-7. doi: 10.1097/01.MP.0000082395.59356.4F.
Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in melanocytic lesions. A series of 10 cutaneous melanomas and 24 benign melanocytic lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle upon Tyne, UK) was scored by an average of the mean labeling intensity; no nuclear staining = 0, weak nuclear staining = 1, moderate = 2, and intense = 3. Ets-1 expression was statistically assessed by the one-way analysis of variance (ANOVA) comparing the mean labeling intensity of melanoma to benign melanocytic nevi. All of the benign melanocytic lesions exhibited negative to weak nuclear staining, with an average mean labeling intensity of 0.4. Melanoma in situ exhibited moderate nuclear staining, for a mean labeling intensity of 2.0, whereas all conventional invasive melanomas exhibited moderate to strong nuclear staining, with a mean labeling intensity of 2.7. Metastatic melanoma exhibited very strong nuclear staining, with a mean labeling intensity of 3.0. Invasive desmoplastic melanoma, like melanoma in situ, showed moderate nuclear staining with a mean labeling intensity of 2.1. There was a trend toward more intense staining with melanoma progression. A statistically significant difference in the mean labeling intensity of Ets-1 was seen between invasive melanoma and benign melanocytic nevi (P <.0001). Ets-1 oncoprotein expression, however, does not distinguish among benign melanocytic lesions. Staining intensity and pattern might be a useful adjunct with histomorphology in distinguishing invasive melanoma from benign melanocytic nevi. Furthermore, Ets-1 expression may be an important pathogenic mechanism and predictor of aggressive biologic behavior of cutaneous melanoma, with a trend toward staining intensity increasing as Clark stage increases.
Ets-1癌蛋白是一种转录因子，已知其可调节许多在细胞外基质重塑和血管生成中起重要作用的基因的表达。Ets-1的上调在多种人类恶性肿瘤中已显示出重要性，并与预后相关。据我们所知，这种癌蛋白尚未在黑素细胞性病变中进行研究。两位皮肤病理学家对一系列10例皮肤黑色素瘤和24例有患者记录的良性黑素细胞性病变进行了独立检查，以确认诊断并进行免疫组化表达分析。Ets-1（英国泰恩河畔纽卡斯尔的诺沃卡斯尔公司）的免疫组化表达通过平均平均标记强度进行评分；无核染色=0，弱核染色=1，中度=2，强阳性=3。通过单因素方差分析（ANOVA）比较黑色素瘤与良性黑素细胞痣的平均标记强度，对Ets-1表达进行统计学评估。所有良性黑素细胞性病变均表现为阴性至弱阳性核染色，平均平均标记强度为0.4。原位黑色素瘤表现为中度核染色，平均标记强度为2.0，而所有传统浸润性黑色素瘤均表现为中度至强阳性核染色，平均标记强度为2.7。转移性黑色素瘤表现为非常强的核染色，平均标记强度为3.0。浸润性促纤维增生性黑色素瘤与原位黑色素瘤一样，表现为中度核染色，平均标记强度为2.1。随着黑色素瘤进展，有染色更强烈的趋势。浸润性黑色素瘤与良性黑素细胞痣之间Ets-1的平均标记强度存在统计学显著差异（P<.0001）。然而，Ets-1癌蛋白表达并不能区分良性黑素细胞性病变。染色强度和模式可能是在区分浸润性黑色素瘤与良性黑素细胞痣时与组织形态学有用的辅助手段。此外，Ets-1表达可能是皮肤黑色素瘤侵袭性生物学行为的重要致病机制和预测指标，随着克拉克分期增加，有染色强度增加的趋势。
